Preventive effect of verapamil and sodium citrate on the formation of postoperative peritoneal adhesion

PURPOSE: Although our knowledge about peritoneal cavity physiology and peritoneal healing mechanism is increasing, postoperative adhesions continue to be a problem for surgeons from different disciplines. In a postmortem study of 298 cases, it was reported that adhesion was found in 67% of patients who had undergone intra-abdominal surgery, and 93% if more thanone operation was performed. Intraabdominal adhesions may cause postoperative morbidityand cost increase due to pain, intestinal obstruction and infertility as they require majorabdominal surgery and prolong hospitalization period. When the literature is examined, it is seen that many experimental, clinical studies and theoretical reports about adhesionprevention have been published since the beginning of the century. Although there are many studies with different agents on adhesion prevention in the current literature, there is still not a standardized treatment for prevention of intraabdominal adhesions. In previous studies, it was reported that sodium citrate inhibited adhesion formation by inhibiting fibrin accumulation and calcium channel blockers were used in animal models considering that calcium is an important component in the inflammatory response to injury and it has been reported to have an adhesion reducing effect. The aim of this study was to investigate the effect of calcium channel blocker (verapamil) and sodium citrate one by one and together in preventing adhesion formation. MATERİAL AND METHOD: Thirty rats were included in the study. Adhesion model was created by abrasion in the cecum (scraping model). Sham group( n=6): Laparatomy Group A; control (abrasion) (n=6): laparatomy + cecum abrasion, Group B; only verapamil (n=6): laparatomy + cecum abrasion + verapamil, Group C; only sodium citrate (n=6): laparatomy + cecum abrasion + sodium citrate, Group D; binary treatment (n=6): laparatomy + cecum abrasion+ verapamil + sodium citrate, totally five groups created. After laparotomy and cecal abrasion, verapamil (diltiazem hydrochloride) intraperitoneally to cover the abdominal cavity - in 10 ml diltiazem, 10 mg/kg saline; sodium citrate 1 ml/kg dose and in the double treatment verapamil + sodium citrate was administered once at the same doses and left for 10 minutes. After seven days, the abdomen was opened by re-laparotomy. The macroscopic adhesions were resected, and the materials were examined under light microscope. The degree of fibrosis and inflammation intensity was evaluated by histomorphologic examination. The degree of fibrosis was determined by the amount of collagen fibres and fibroblasts. Inflammation intensity was evaluated according to the amount of lymphocytes, plasma cells, eosinophils and neutrophils. The evaluation was made by a pathologist who was unaware of the method and the groups (blind evaluation). Histopathological Fibrosis Classification Inflammation Classificaiton Grade-0: No fibrosis Grade-0: No inflammation Grade-1: Mild fibrosis Grade-1: Mild inflammation Grade-2: Moderate fibrosis Grade-2: Moderate inflammation Grade-3: Severe fibrosis Grade-3: Severe inflammation RESULTS: According to the study groups, there was a statistically significant difference in the development of adhesion (p = 0.003). The development of adhesions in groups B and D was less common (p = 0.015 and p = 0.015). Although the rate of adhesion was lower in Group C than Group A, the difference was not statistically significant (p = 0.061). There was no statistically significant difference between Group B and C and between Group C and D (p> 0,999). Table 1 and Figure 1 show the frequency distributions in terms of adhesion development according to the study groups CONCLUSION: Verapamil reduces adhesion formation. Sodium citrate has a similar effect. However, concomitant use of verapamil with sodium citrate does not provide an aditive effect.